Viral Genome Replication

pp 527-548


Viral RNA Polymerase Inhibitors

  • Todd ApplebyAffiliated withGilead Sciences, Inc.
  • , I-hung ShihAffiliated withGilead Sciences, Inc.
  • , Weidong ZhongAffiliated withGilead Sciences, Inc. Email author 

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Infections by RNA viruses continue to exist as significant public health problems worldwide. In response to the urgent need for safer and more efficacious treatment options against infections caused by RNA viruses, the pharmaceutical and biotechnology industries have devoted significant efforts over the last two decades to discovering and developing new antiviral agents. As the primary viral enzyme responsible for genome replication and transcription, RNA-dependent RNA polymerases (RdRps) emerged early and remained as one of the most promising targets for therapeutic intervention of RNA virus infections. Advances in both basic research and drug discovery technology have resulted in the identification of a significant number of nucleoside (NIs) and non-nucleoside inhibitors (NNIs) of viral RdRps. In this chapter, we will focus our attention on various classes of viral RdRp inhibitors, with main emphases on those of hepatitis C virus (HCV) due to its significant unmet medical need. Recent progress in understanding their mechanism of action, antiviral activity profiles, and emergence of drug resistance mutations will be discussed.